The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Science. 2018 Apr 20;360(6386). doi: 10.1126/science.aao1729.
To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.
为了系统地探索复杂的遗传相互作用，我们构建了约 20 万个酵母三突变体，并对负三基因相互作用进行了评分。我们选择了跨越广泛生物过程的双突变体查询基因，这些基因涵盖了全局双基因相互作用网络的一系列定量特征，并测试了与第三个突变的遗传相互作用。三基因相互作用通常发生在功能相关的基因之间，而必需基因则是三基因网络的枢纽。尽管它们具有功能富集性，但三基因相互作用往往将不同生物过程的基因联系起来，其强度比双基因相互作用弱。我们估计，全局三基因相互作用网络的规模约为全局双基因网络的 100 倍，这突出了复杂遗传相互作用可能会影响遗传生物学，包括基因型到表型的关系。
